We are studying the molecular events underlying normal and abnormal mitosis in mammalian cells. We have identified a protein found in Chinese hamster ovary cells which can induce the initiation of mitotic events when injected into X. laevis oocytes. Through a combination of physical and chromatographic steps, we have been able to significantly purify this protein and show that it must be phosphorylated to exert its action. Current efforts are aimed at further purification of the protein as well as molecular cloning of the gene coding for it. We have also initiated a study designed to document genetic changes associated with the abnormal mitosis that characterizes cancer. These studies have demonstrated a striking change in DNA methylation in human cancer cells when compared with their normal counterparts. These changes were widespread, progressive and heterogeneous and, hence, have many features linking such changes to the abnormal gene expression found in cancer. Efforts are being made to identify other genomic changes (particularly rearrangements) that commonly occur in human cancer cells.